skip to main content

Attention:

The NSF Public Access Repository (PAR) system and access will be unavailable from 8:00 PM ET on Friday, March 21 until 8:00 AM ET on Saturday, March 22 due to maintenance. We apologize for the inconvenience.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Tunable, bacterio-instructive scaffolds made from functional graphenic materials
The balance of bacterial populations in the human body is critical for human health. Researchers have aimed to control bacterial populations using antibiotic substrates. However, antibiotic materials that non-selectively kill bacteria can compromise health by eliminating beneficial bacteria, which leaves the body vulnerable to colonization by harmful pathogens. Due to their chemical tunablity and unique surface properties, graphene oxide (GO)-based materials – termed “functional graphenic materials” (FGMs) – have been previously designed to be antibacterial but have the capacity to actively adhere and instruct probiotics to maintain human health. Numerous studies have demonstrated that negatively and positively charged surfaces influence bacterial adhesion through electrostatic interactions with the negatively charged bacterial surface. We found that tuning the surface charge of FGMs provides an avenue to control bacterial attachment without compromising vitality. Using E. coli as a model organism for Gram-negative bacteria, we demonstrate that negatively charged Claisen graphene (CG), a reduced and carboxylated FGM, is bacterio-repellent through electrostatic repulsion with the bacterial surface. Though positively charged poly- l -lysine (PLL) is antibacterial when free in solution by inserting into the bacterial cell wall, here, we found that covalent conjugation of PLL to CG (giving PLL n -G) masks the antimicrobial activity of PLL by restricting polypeptide mobility. This allows the immobilized positive charge of the PLL n -Gs to be leveraged for E. coli adhesion through electrostatic attraction. We identified the magnitude of positive charge of the PLL n -G conjugates, which is modulated by the length of the PLL peptide, as an important parameter to tune the balance between the opposing forces of bacterial adhesion and proliferation. We also tested adhesion of Gram-positive B. subtilis to these FGMs and found that the effect of FGM charge is less pronounced. B. subtilis adheres nondiscriminatory to all FGMs, regardless of charge, but adhesion is scarce and localized. Overall, this work demonstrates that FGMs can be tuned to selectively control bacterial response, paving the way for future development of FGM-based biomaterials as bacterio-instructive scaffolds through careful design of FGM surface chemistry.  more » « less
Award ID(s):
1905665
PAR ID:
10301672
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Biomaterials Science
Volume:
9
Issue:
7
ISSN:
2047-4830
Page Range / eLocation ID:
2467 to 2479
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ( , Applied Surface Science)
    Frederiksberg, Dr_Henrik_Rudolph (Ed.)
    Wound dressings based on natural materials, such as fish skin, represent an important strategy for the treatment of burns. Despite their utility, contamination of these natural materials with bacteria (planktonic and biofilm forms) introduces significant risks to patients under treatment. This disadvantage can be overcome by modifying the material’s surface to prevent bacterial deposition through chemical or physical interactions. In this work, functional graphenic materials (FGM) with tunable surface charges were incorporated into tilapia (Oreochromis niloticus) fish skin as a part of a strategy to control the biofilm adhesion on surfaces. The antibiofilm activity was evaluated against S. aureus and K. pneumoniae due to the biofilm-forming properties of these bacterial strains. FGM-modified tilapia skin samples possess a strong capacity to reduce biofilm formation on the tilapia fish skin with a higher antibiofilm activity against Gram-positive bacteria, compared to Gram-negative bacteria. Negatively charged FGMs were more effective than positively charged FGMs in preventing biofilm formation on the impregnated tilapia skin xenografts: negatively charged Claisen graphene achieved an 88.8% reduction in biofilm formation on the tilapia skin. Overall, this study demonstrates the utility of FGM-impregnated tilapia skins as a treatment for burn wounds due to their ability to modulate bacterial adhesion. 
    more » « less
  2. ; ; ; ; ; ( , Polymer International)
    Abstract

    Each year, thousands of patients die from antimicrobial‐resistant bacterial infections that fail to respond to conventional antibiotic treatment. Antimicrobial polymers are a promising new method of combating antibiotic‐resistant bacterial infections. We have previously reported the synthesis of a series of narrow‐spectrum peptidomimetic antimicrobial polyurethanes that are effective against Gram‐negative bacteria, such asEscherichia coli; however, these polymers are not effective against Gram‐positive bacteria, such asStaphylococcus aureus. With the aim of understanding the correlation between chemical structure and antibacterial activity, we have subsequently developed three structural variants of these antimicrobial polyurethanes using post‐polymerization modification with decanoic acid and oleic acid. Our results show that such modifications converted the narrow‐spectrum antibacterial activity of these polymers into broad‐spectrum activity against Gram‐positive species such asS. aureus, however, also increasing their toxicity to mammalian cells. Mechanistic studies of bacterial membrane disruption illustrate the differences in antibacterial action between the various polymers. The results demonstrate the challenge of balancing antimicrobial activity and mammalian cell compatibility in the design of antimicrobial polymer compositions. © 2019 Society of Chemical Industry

     
    more » « less
  3. ; ; ; ; ( , Journal of Materials Chemistry B)
    Due to the emergence of wide-spread infectious diseases, there is a heightened need for antimicrobial and/or antifouling coatings that can be used to prevent infection and transmission in a variety of applications, ranging from healthcare devices to public facilities. While antimicrobial coatings kill pathogenic bacteria upon contact with the surface, the antimicrobial function alone often lacks long-term effectiveness due to the accumulation of dead cells and their debris on the surface, thus reducing the performance of the coating over time. Therefore, it is desirable to develop coatings with the dual functions of antimicrobial efficacy and fouling resistance, in which antifouling coatings provide the added benefit of preventing the adhesion of dead cells and debris. Leveraging the outstanding antifouling properties of zwitterionic coatings, we synthesized copolymers with this antimicrobial-antifouling dual function by immobilizing lysozyme, a common antimicrobial enzyme, to the surface of a pyridinium-based zwitterionic copolymer. Specifically, poly(4-vinylpyridine- co -pentaflurophenyl methacrylate- co -divinyl benzene) [P(4VP-PFPMA-DVB)] thin films were synthesized by an all-dry vapor deposition technique, initiated Chemical Vapor Deposition, and derivatized using 1,3-propane sultone to obtain sulfobetaine moieties. Lysozyme, known to hydrolyze polysaccharides in the cell wall of Gram-positive bacteria, was immobilized by forming amide bonds with the copolymer coating via nucleophilic substitution of the pentafluorophenyl group. The antifouling and antibacterial performance of the novel lysozyme-zwitterionic coating was tested against Gram-positive Bacillus subtilis and Gram-negative Pseudomonas aeruginosa . A reduction in surface adhesion of 87% was achieved for P. aeruginosa , and of 75% for B. subtilis , when compared to a common poly(vinyl chloride) surface. The lysozyme-zwitterionic coating also deactivated 67% of surface-attached Gram-positive bacteria, B. subtilis . This novel dual-function material can produce anti -infection surfaces for medical devices and surgical tools, personal care products, and surfaces in public facilities. 
    more » « less
  4. ; ; ; ; ; ( , Biosensors)

    As membrane-mediated antibiotic resistance continues to evolve in Gram-positive bacteria, the development of new approaches to elucidate the membrane properties involved in antibiotic resistance has become critical. Membrane vesicles (MVs) secreted by the cytoplasmic membrane of Gram-positive bacteria contain native components, preserving lipid and protein diversity, nucleic acids, and sometimes virulence factors. Thus, MV-derived membrane platforms present a great model for Gram-positive bacterial membranes. In this work, we report the development of a planar bacterial cytoplasmic membrane-based biosensor using MVs isolated from the Bacillus subtilis WT strain that can be coated on multiple surface types such as glass, quartz crystals, and polymeric electrodes, fostering the multimodal assessment of drug–membrane interactions. Retention of native membrane components such as lipoteichoic acids, lipids, and proteins is verified. This biosensor replicates known interaction patterns of the antimicrobial compound, daptomycin, with the Gram-positive bacterial membrane, establishing the applicability of this platform for carrying out biophysical characterization of the interactions of membrane-acting antibiotic compounds with the bacterial cytoplasmic membrane. We report changes in membrane viscoelasticity and permeability that correspond to partial membrane disruption when calcium ions are present with daptomycin but not when these ions are absent. This biomembrane-based biosensing platform enables an assessment of membrane biophysical characteristics during exposure to antibiotic drug candidates to aid in identifying compounds that target membrane disruption as a mechanism of action.

     
    more » « less
  5. ; ; ; ; ; ; ; ( , Chemical Science)
    Molecular-level understanding of nanomaterial interactions with bacterial cell surfaces can facilitate design of antimicrobial and antifouling surfaces and inform assessment of potential consequences of nanomaterial release into the environment. Here, we investigate the interaction of cationic nanoparticles with the main surface components of Gram-positive bacteria: peptidoglycan and teichoic acids. We employed intact cells and isolated cell walls from wild type Bacillus subtilis and two mutant strains differing in wall teichoic acid composition to investigate interaction with gold nanoparticles functionalized with cationic, branched polyethylenimine. We quantified nanoparticle association with intact cells by flow cytometry and determined sites of interaction by solid-state 31 P- and 13 C-NMR spectroscopy. We find that wall teichoic acid structure and composition were important determinants for the extent of interaction with cationic gold nanoparticles. The nanoparticles interacted more with wall teichoic acids from the wild type and mutant lacking glucose in its wall teichoic acids than those from the mutant having wall teichoic acids lacking alanine and exhibiting more restricted molecular motion. Our experimental evidence supports the interpretation that electrostatic forces contributed to nanoparticle–cell interactions and that the accessibility of negatively charged moieties in teichoic acid chains influences the degree of interaction. The approaches employed in this study can be applied to engineered nanomaterials differing in core composition, shape, or surface functional groups as well as to other types of bacteria to elucidate the influence of nanoparticle and cell surface properties on interactions with Gram-positive bacteria. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email